Lactate reshapes the tumor microenvironment (TME) through complex communication between cancer and stromal cells. However, it remains undefined whether lactate mediates the interaction between pancreatic cancer (PC) cells and pancreatic stellate cells (PSCs), a significant TME component driving tumorigenesis. This study elucidates the metabolic crosstalk between PC cells and PSCs underlying lactate-driven tumor progression. Our findings demonstrate that PC cells serve as the primary lactate source in the TME, where lactate induces PSC activation through an autophagy-dependent mechanism mediated by protein lactylation. This activation cascade subsequently upregulates programmed cell death-1 (PD-1) expression in CD8+ T cells, promoting immune evasion. Notably, AZD3965, a specific MCT1 inhibitor, sensitizes orthotopic PC to PD-1 blockade, effectively inhibiting tumor development. Mechanistically, MCT1-mediated lactate influx activates PSCs by inducing lactylation of lysine residues K356 and K781 on Vps34, a key autophagy regulator. Moreover, activated PSCs secrete CXCL9/CXCL10, which upregulates PD-1 expression in CD8+ T cells via the CXCR3/STAT3 pathway. This study establishes lactate as a crucial TME signaling molecule orchestrating PSC activation and an immunosuppressive microenvironment, providing compelling evidence for combining MCT1 inhibition with immune checkpoint blockade for pancreatic cancer.

Circulating linoleic acid (LA) levels have been reported to be associated with various metabolic outcomes. However, the role of LA and its interplay with gut microbiota in gestational diabetes mellitus (GDM) remains unclear. This study aimed to investigate the longitudinal association between circulating LA levels during pregnancy and the risk of GDM, and the potential role of gut microbiota. A nested case–control study was conducted within the ongoing Tongji-Huaxi-Shuangliu Birth Cohort in Chengdu, China. Blood and fecal samples were collected during early and middle pregnancy from 807 participants. GDM was diagnosed in middle pregnancy using the International Association of Diabetes and Pregnancy Study Groups criteria. Plasma LA levels were measured using gas chromatography-mass spectrometry, and gut microbiota was analyzed through 16S rRNA gene sequencing and shotgun metagenomic sequencing. A two-sample Mendelian randomization study was conducted using data from the IEU OpenGWAS database and the FinnGen consortium. Elevated plasma LA levels were associated with a lower risk of GDM in both early (P for trend = 0.002) and middle pregnancy (P for trend = 0.02). Consistently, Mendelian randomization analysis revealed that each unit increase in LA was associated with a 16

Objectives: To investigate the role of the intestinal flora and metabolites in the development of hyperuricemic renal injury in chronic kidney disease (CKD).Methods: Unilaterally nephrectomized mice were fed with adenine and potassium oxonate for 9 weeks. HE staining combined with plasma biochemical indicators was used to evaluate renal pathological and functional changes. We conducted 16S rRNA sequencing and untargeted metabolomics on feces and plasma samples to reveale changes in intestinal microbiota and metabolites.Result: Our analysis revealed significant differences in 15 bacterial genera, with 7 being upregulated and 8 being downregulated. Furthermore, metabolomic analysis revealed changes in the distribution of amino acid and biotin metabolites in basic metabolic pathways in both feces and serum. Specifically, differentially abundant metabolites in feces were associated primarily with histidine metabolism; the biosynthesis of phenylalanine, tyrosine, and tryptophan; and tyrosine metabolism. In plasma, the differentially abundant metabolites were involved in multiple metabolic pathways, including aminoacyl-tRNA biosynthesis; glycine, serine, and threonine amino acid metabolism; valine, leucine, and isoleucine biosynthesis; tyrosine biosynthesis and metabolism; biotin metabolism; and taurine and hypotaurine metabolism. Furthermore, correlation analysis revealed that Akkermansia, UCG-005, Lachnospiraceae_NK4A136_group, Lactococcus, and Butymonas were associated with various differentially abundant metabolites as well as renal function, oxidative stress, and mitophagy. The changes in the intestinal flora observed in hyperuricemia may lead to imbalances in amino acid and biotin metabolism in both the intestine and host, ultimately affecting oxidative stress and mitophagy in mice and accelerating the progression of CKD.Conclusion: Our findings provide insights into a potential pathogenic mechanism by which hyperuricemia exacerbates renal injury in mice with renal insufficiency. Understanding these pathways may offer new therapeutic strategies for managing hyperuricemic renal injury in CKD patients.

The intestinal microbiota comprises approximately 1013-1014 species of bacteria and plays a crucial role in host metabolism by facilitating various chemical reactions. Secondary bile acids (BAs) are key metabolites produced by gut microbiota.Initially synthesized by the liver, BA undergoes structural modifications through the activity of various intestinal microbiota enzymes, including eukaryotic, bacterial, and archaeal enzymes. These modified BA then activate specific receptors that regulate multiple metabolic pathways in the host, such as lipid and glucose metabolism, energy balance, inflammatory response, and cell proliferation and death. Recent attention has been given to intestinal flora disorders in diabetic kidney disease (DKD), where activation of BA receptors has shown promise in alleviating diabetic kidney damage by modulating renal lipid metabolism and mitochondrial production. Imbalances in the intestinal flora can influence the progression of DKD through the regulation of bile acid and its receptor pathways. This review aims to propose a mechanism involving the gut-BA-diabetes and nephropathy axes with the goal of optimizing new strategies for treating DKD.

Background Immunoglobulin A nephropathy (IgAN) is a major cause of primary glomerulonephritis characterized by mesangial deposits of galactose-deficient IgA1 (Gd-IgA1). Toll-like receptors (TLRs), particularly TLR4, are involved in the pathogenesis of IgAN. The role of gut microbiota on IgAN patients was recently investigated. However, whether gut microbial modifications of Gd-IgA1 through TLR4 play a role in IgAN remains unclear.Methods We recruited subjects into four groups, including 48 patients with untreated IgAN, 22 treated IgAN patients (IgANIT), 22 primary membranous nephropathy and 31 healthy controls (HCs). Fecal samples were collected to analyze changes in gut microbiome. Gd-IgA1 levels, expression of TLR4, B-cell stimulators and intestinal barrier function were evaluated in all subjects. C57BL/6 mice were treated with a broad-spectrum antibiotic cocktail to deplete the gut microbiota and then gavaged with fecal microbiota transplanted from clinical subjects of every group. Gd-IgA1 and TLR4 pathway were detected in peripheral blood mononuclear cells (PBMCs) from IgAN and HCs co-incubated with lipopolysaccharide (LPS) and TLR4 inhibitor.Results Compared with the other three groups, different compositions and decreased diversity demonstrated gut dysbiosis in the untreated IgAN group, especially the enrichment of Escherichia-Shigella. Elevated Gd-IgA1 levels were found in untreated IgAN patients and correlated with gut dysbiosis, TLR4, B-cell stimulators, indexes of intestinal barrier damage and proinflammatory cytokines. In vivo, mice colonized with gut microbiota from IgAN and IgANIT patients mimicked the IgAN phenotype with the activation of TLR4/MyD88/nuclear factor-kappa B pathway and B-cell stimulators in the intestine, and had with enhanced proinflammatory cytokines. In vitro, LPS activated TLR4/MyD88/NF-kappa B pathway, B-cell stimulators and proinflammatory cytokines in PBMCs of IgAN patients. This process may induce the overproduction of Gd-IgA1, which was inhibited by TLR4 inhibitors.Conclusions Our results illustrated that the gut-kidney axis is involved in the pathogenesis of IgAN. Gut dysbiosis could stimulate the overproduction of Gd-IgA1 via TLR4 signaling pathway production and B-cell stimulators. Graphical Abstract

Introduction: Numerous research works have shown that serum Gal-deficient (Gd) IgA1 levels are increased in IgA nephropathy (IgAN) patients and these levels are a dangerous risk factor for IgAN. A relationship between the gut microbiota and IgAN has been reported. Whether the gut microbiota participates in the pathogenesis of IgAN was still controversial. Methods: We evaluated changes in the gut flora and the levels of Gd-IgA1 in IgAN patients and healthy controls (HCs). We investigated the Gd-IgA1 levels in both blood and urine specimens. C57BL/6 mice were given a broad-spectrum antibiotic cocktail to deplete the endogenous gut flora. We established a model of IgAN in pseudosterile mice and investigated the expression of the markers of intestinal permeability, inflammation, and local immune responses. Results: Studies have shown that the levels of certain gut flora differ between IgAN patients and HCs. Moreover, elevated Gd-IgA1 levels were found in both the serum and urine. Interestingly, Coprococcus, Dorea, Bifidobacterium, Blautia, and Lactococcus, selected from 10 candidate biomarkers to predict risk in IgAN patients according to random forest analysis, were inversely associated with urinary Gd-IgA1 levels. Notably, the urine level of Gd-IgA1 could best distinguish IgAN patients from HCs. Additionally, the degree of kidney damage in pseudosterile mice with IgAN was more severe than that in mice with IgAN. Furthermore, the markers of intestinal permeability were significantly elevated in pseudosterile IgAN mice. Moreover, the inflammation responses (TLR4, MyD88, and NF-κB in intestinal and renal tissues; TNF-α and IL-6 in serum) and local immune responses (BAFF and APRIL in intestinal tissue) were upregulated in pseudosterile IgAN mice. Conclusions: The urine Gd-IgA1 level may be as a biomarker for the early screening of potential IgAN, and gut microbiota dysbiosis was demonstrated in IgAN, which might involve the dysfunction of the mucosal barrier, inflammation, and local immune responses.

Recent advances in next-generation sequencing technologies and improvements in bioinformatics have expanded the scope of microbiome analysis as a forensic tool. Microbiome research is concerned with the study of the compositional profile and diversity of microbial flora as well as the interactions between microbes, hosts, and the environment. It has opened up many new possibilities for forensic analysis. In this review, we discuss various applications of microbiome in forensics, including identification of individuals, geolocation inference, and post-mortem interval (PMI) estimation.

Background and aimsEstimated pulse wave velocity (ePWV) and systemic inflammatory response index (SIRI) have been recently investigated as a marker of arterial stiffness and a novel systemic inflammatory indicator. This study aims to examine the independent and combined association of ePWV and SIRI with incident stroke and its subtypes.MethodsData of the Dongfeng-Tongji cohort study was analyzed for 9,154 middle-aged and older adults, who were free of cardiovascular disease and cancer and were followed up to document incident stroke. But their association with incident stroke events and its subtypes have not been well studied. Multivariable adjusted Cox regression models were used to determine the independent and combined association of ePWV and SIRI with incident stroke events.ResultsOver a 7.22-year follow-up, the cohort documented 491 stroke cases (387 ischemic stroke and 104 hemorrhagic stroke). The multivariate adjusted model showed that with each one-unit increase in the level of ePWV, the corresponding hazard ratios (HRs) (95% CI) for total stroke, ischemic stroke, and hemorrhagic stroke were 1.53 (95% CI, 1.23–1.90), 1.42 (95% CI, 1.11–1.83), and 1.92 (95% CI, 1.21–3.03), respectively. Similarly, with each one-unit increase in log-transformed levels of SIRI, the corresponding HRs (95% CI) for total stroke, ischemic stroke, and hemorrhagic stroke were 1.23 (95% CI,1.04–1.47), 1.16 (95% CI, 0.96–1.41), and 1.52 (95% CI, 1.05–2.20), respectively. There appeared to be a combined effect of ePWV and SIRI on stroke; Participants with high levels of both ePWV and SIRI had a higher risk of total stroke and hemorrhagic stroke, with multiple adjusted HR of 2.43 (95% CI, 1.09–5.42). Additionally, the incorporation of ePWV in addition to traditional cardiovascular risk factors significantly improved the predictive accuracy for total stroke with C statistic increased from 0.684 (95% CI, 0.661–0.707) to 0.687 (95% CI, 0.664–0.710; x2 = 6.65; p for difference = 0.010), and (suggestively) for ischemic stroke with C statistic increased from 0.684 (95% CI, 0.659–0.71) to 0.691(95% CI, 0.666–0.717; x2 = 3.13, p for difference = 0.077), respectively.ConclusionsThe presence of both high ePWV and SIRI individually, as well as together, was found to be associated with an increased incidence of stroke. The combined stroke risk assessment using these two indicators could potentially improve non-invasive assessment and treatment strategies for high-risk patients, as these indicators are easily accessible in clinical practice.

Though gut microbiome disturbance may be involved in the etiology of gestational diabetes mellitus (GDM), data on the gut microbiome's dynamic change during pregnancy and associations with gestational glucose metabolism are still inadequate. In this prospective study comprising 120 pairs of GDM patients and matched pregnant controls, a decrease in the diversity of gut microbial species and changes in the microbial community composition with advancing gestation are found in controls, while no such trends are observed in GDM patients. Multivariable analysis identifies 10 GDM-related species (e.g., Alistipes putredinis), and the integrated associations of these species with glycemic traits are modified by habitual intake of fiber-rich plant foods. In addition, the microbial metabolic potentials related to fiber fermentation (e.g., mannan degradation pathways) and their key enzymes consistently emerge as associated with both GDM status and glycemic traits. Microbial features especially those involved in fiber fermentation, provide an incremental predictive value in a prediction model with established risk factors of GDM. These data suggest that the gut microbiome remodeling with advancing gestation is different in GDM patients compared with controls, and dietary fiber fermentation contributes to the influence of gut microbiome on gestational glycemic regulation.

The main treatment for renal anemia in end-stage renal disease (ESRD) patients on hemodialysis is erythropoiesis (EPO). EPO hyporesponsiveness (EH) in dialysis patients is a common clinical problem, which is poorly understood. Recent searches reported that gut microbiota was closely related to the occurrence and development of ESRD. This study aims to explore the changes in gut microbiota between ESRD patients with different responsiveness to EPO treatment. We compared the gut microbiota from 44 poor-response (PR) and 48 good-response (GR) hemodialysis patients treated with EPO using 16S rDNA sequencing analysis. The results showed that PR patients displayed a characteristic composition of the gut microbiome that clearly differed from that of GR patients. Nine genera (Neisseria, Streptococcus, Porphyromonas, Fusobacterium, Prevotella_7, Rothia, Leptotrichia, Prevotella, Actinomyces) we identified by Lasso regression and ROC curves could excellently predict EH. In contrast, five genera (Faecalibacterium, Citrobacter, Bifidobacterium, Escherichia-Shigella, Bacteroides) identified by the same means presented a protective effect against EH. Analyzing the correlation between these biomarkers and clinical indicators, we found that gut microbiota may affect response to EPO through nutritional status and parathyroid function. These findings suggest that gut microbiota is altered in hemodialysis patients with EH, giving new clues to the pathogenesis of renal anemia.

Tanc2 is a large multi-domain postsynaptic scaffold protein mainly expressed in the brain. In humans, tanc2 mutations have been associated with autism spectrum disorder (ASD) and other related neurodevelopmental disorders. However, the role of tanc2 in neurodevelopment and in controlling behaviors are not fully understood. Here, we generated and characterized a tanc2 knockout allele in zebrafish. Loss of tanc2 increases the larval brain size and body length by promoting proliferation and inhibiting apoptosis. We observed that the glutamatergic neuron population is significantly increased in tanc2 mutants while the GABAergic and the glycinergic neurons are not affected, suggesting that an excitatory/inhibitory (E/I) imbalance. Indeed, the tanc2 knockout larvae exhibited increase sleep. In adult zebrafish, the mutants display anxiolytic-behavior, reduced aggression, and impaired social preference. The alterations in these behaviors are phenotypically similar to the ASD patients carrying tanc2 mutations. Therefore, the tanc2 knockout allele could serve as a valuable model to further study the role of tanc2 in the nervous system.

Epidemiological studies have revealed associations between several temperature parameters and allergic rhinitis (AR). However, few studies have reported the association of AR with daily temperature variability, which indicates both short-term intra- and interday temperature changes. This study aimed to analyze associations between temperature variability and initial outpatient visits for AR. The analysis was conducted with an over-dispersed Poisson model using daily time-series data on temperature and the number of initial AR outpatients from 2013 to 2015 in Changchun, China. The composite index of temperature variability was derived by calculating the standard deviation of daily minimum temperature and maximum temperature over exposure days. Stratified analysis by season was also conducted. There were 23,344 AR outpatients during the study period. In the total period, per 1 °C increase in temperature variability at 0–2 days (TV0–2), 0–3 days (TV0–3), and 0–4 days (TV0–4) was associated with a 4.03% (95% CI: 0.91–7.25%), 4.40% (95% CI: 0.95–7.97%), and 4.12% (95% CI: 0.38–8.01%) increase in the number of AR outpatients, respectively. When stratified by season, the strongest effect was shown in spring. Our results suggested that temperature variability was associated with increased initial outpatient visits for AR, which may provide helpful implications for formulating public health policies to reduce adverse health impacts of unstable temperature.

Background and aims: Systemic immune-inflammation index (SII) has been recently investigated as a novel inflammatory and prognostic marker. SII may be used as an indicator reflecting the progressive inflammatory process in atherosclerosis, although its link to incident cardiovascular disease (CVD) has not been examined in previous studies. This study aims to prospectively assess the association of SII with incident CVD and its main subtypes in Chinese adults. Methods: Using data from the Dongfeng-Tongji cohort study, 13,929 middle-aged and older adults with a mean age of 62.56 years (range 35?91 years), who were free of CVD and cancer, were included for analysis. The baseline study was conducted in Shiyan city, Hubei province from 2008 to 2009. The SII was calculated as platelet count (/L) ? neutrophil count (/L)/lymphocyte count (/L). Cox regression models were used to examine the associations of SII with incident CVD, including stroke and coronary heart disease (CHD). Results: Over a median 8.28 years (maximum 8.98 years) of follow-up, 3386 total CVD cases, including 801 stroke cases and 2585 total CHD cases, were identified. In multivariable Cox regression analyses, higher levels of log-transformed SII were significantly associated with total stroke (HR 1.224, 95% CI 1.065?1.407) and ischemic stroke (HR 1.234, 95% CI 1.055?1.442). For those participants with the highest quartiles of SII versus the lowest quartiles of SII, the HRs were 1.358 (95% CI 1.112?1.658) for total stroke, 1.302 (95% CI 1.041?1.629) for ischemic stroke, and 1.600 (95% CI 1.029?2.490) for hemorrhagic stroke. Conclusions: SII may serve as a useful marker to elucidate the role of the interaction of thrombocytosis, inflammation, and immunity in the development of cerebrovascular diseases in the middle-aged and elderly population.

目的寻找饮酒与不饮酒的成年男性肠道菌群的差异,探讨饮酒对健康成年男性肠道菌群的影响。方法收集前往湖北省人类精子库进行捐精前精液质量筛查的健康成年男性的粪便样本50例（饮酒组37例,不饮酒组13例）,提取DNA后进行16S rRNA基因扩增子测序。结果饮酒组的肠道菌群α多样性与不饮酒组的差异无统计学意义但β多样性差异有统计学意义（PERMANOVA,F=0.544 9,P=0.014 0）。饮酒组中出现放线菌门和双歧杆菌科的显著富集,且出现了科与属水平种类的减少,相比不饮酒组少了12个菌科和27个菌属。通过差异性菌群分析发现放线菌门下Bifidobacterium spp.和厚壁菌门下的Blautia spp.、Dorea spp.和Ruminococcus spp.在饮酒组富集。结论饮酒可能会改变健康成年男性的肠道菌群,饮酒组与不饮酒组人群的肠道菌群在群落结构上存在差异。

Malignant pleural mesothelioma (MPM) is a highly aggressive cancer with short survival time. Unbalanced competing endogenous RNAs (ceRNAs) have been shown to participate in the tumor pathogenesis and served as biomarkers for the clinical prognosis. However, the comprehensive analyses of the ceRNA network in the prognosis of MPM are still rarely reported. In this study, we obtained the transcriptome data of the MPM and the normal samples from TCGA, EGA, and GEO databases and identified the differentially expressed (DE) mRNAs, lncRNAs, and miRNAs. The functions of the prognostic genes and the overlapped DEmRNAs were further annotated by the multiple enrichment analyses. Then, the targeting relationships among lncRNA–miRNA and miRNA–mRNA were predicted and calculated, and a prognostic ceRNA regulatory network was established. We included the prognostic 73 mRNAs and 13 miRNAs and 26 lncRNAs into the ceRNA network. Moreover, 33 mRNAs, three miRNAs, and seven lncRNAs were finally associated with prognosis, and a model including seven mRNAs, two lincRNAs, and some clinical factors was finally established and validated by two independent cohorts, where CDK6 and SGMS1-AS1 were significant to be independent prognostic factors. In addition, the identified co-expressed modules associated with the prognosis were overrepresented in the ceRNA network. Multiple enrichment analyses showed the important roles of the extracellular matrix components and cell division dysfunction in the invasion of MPM potentially. In summary, the prognostic ceRNA network of MPM was established and analyzed for the first time and these findings shed light on the function of ceRNAs and revealed the potential prognostic and therapeutic biomarkers of MPM.

At birth, human infants are poised to survive in harsh, hostile conditions. An understanding of the state of newborn skin development and maturation is key to the maintenance of health, optimum response to injury, healing and disease. The observational study collected full-thickness newborn skin samples from 27 infants at surgery and compared them to skin samples from 43 adult sites protected from ultraviolet radiation exposure, as the standard for stable, mature skin. Transcriptomics profiling and gene set enrichment analysis were performed. Statistical analysis established over 25,000 differentially regulated probe sets, representing 10,647 distinct genes, in infant skin compared to adult skin. Gene set enrichment analysis showed a significant increase in 143 biological processes (adjusted p < 0.01) in infant skin, versus adult skin samples, including extracellular matrix (ECM) organization, cell adhesion, collagen fibril organization and fatty acid metabolic process. ECM organization and ECM structure organization were the biological processes in infant skin with the lowest adjusted P-value. Genes involving epidermal development, immune function, cell differentiation, and hair cycle were overexpressed in adults, representing 101 significantly enriched biological processes (adjusted p < 0.01). The processes with the highest significant difference were skin and epidermal development, e.g., keratinocyte differentiation, keratinization and cornification intermediate filament cytoskeleton organization and hair cycle. Enriched Gene Ontology (GO) biological processes also involved immune function, including antigen processing and presentation. When compared to ultraviolet radiation-protected adult skin, our results provide essential insight into infant skin and its ability to support the newborn’s preparedness to survive and flourish, despite the infant’s new environment laden with microbes, high oxygen tension and potential irritants. This fundamental knowledge is expected to guide strategies to protect and preserve the features of unperturbed, young skin.

We read with great interest the recent article in Atherosclerosis by Xu et al. [ [1] Xu M. Chen R. Liu X. et al. Systemic immune-inflammation index and incident cardiovascular diseases among middle-aged and elderly Chinese adults: the Dongfeng-Tongji cohort study. Atherosclerosis. 2021; 323: 20-29 Abstract Full Text Full Text PDF PubMed Scopus (5) Google Scholar ]. In a large prospective study comprising 13,929 middle age and elderly individuals of Chinese descent, they showed that the systemic immune-inflammation index (SII), the product of the neutrophil count x platelet count x lymphocyte count, predicted total stroke, ischemic stroke and hemorrhagic stroke over a median follow-up of 8.3 years using multivariate Cox regression analyses [ [1] Xu M. Chen R. Liu X. et al. Systemic immune-inflammation index and incident cardiovascular diseases among middle-aged and elderly Chinese adults: the Dongfeng-Tongji cohort study. Atherosclerosis. 2021; 323: 20-29 Abstract Full Text Full Text PDF PubMed Scopus (5) Google Scholar ]. Although there was a threefold increase in coronary heart disease (CAD), SII did not predict CAD or acute coronary syndromes (ACS). The increase in ischemic stroke did not appear to be significant following exclusion of patients with abnormal white blood cell counts (WBC) p = 0.05. Interestingly, although lymphocyte levels were significantly decreased, they were used in the numerator in computing SII. In addition, no analyses appear to have been undertaken for the significant high density lipoprotein cholesterol (HDL-C) levels across quartiles.

Aims We aimed to assess the association between gut bacterial biomarkers during early pregnancy and subsequent risk of gestational diabetes mellitus (GDM) in Chinese pregnant women. Methods Within the Tongji-Shuangliu Birth Cohort study, we conducted a nested case-control study among 201 incident GDM cases and 201 matched controls. Fecal samples were collected during early pregnancy (at 6-15 weeks), and GDM was diagnosed at 24 to 28 weeks of pregnancy. Community DNA isolated from fecal samples and V3-V4 region of 16S rRNA gene amplicon libraries were sequenced. Results In GDM cases versus controls, Rothia, Actinomyces, Bifidobacterium, Adlercreutzia, and Coriobacteriaceae and Lachnospiraceae spp. were significantly reduced, while Enterobacteriaceae, Ruminococcaceae spp., and Veillonellaceae were overrepresented. In addition, the abundance of Staphylococcus relative to Clostridium, Roseburia, and Coriobacteriaceae as reference microorganisms were positively correlated with fasting blood glucose, 1-hour and 2-hour postprandial glucose levels. Adding microbial taxa to the base GDM prediction model with conventional risk factors increased the C-statistic significantly (P < 0.001) from 0.69 to 0.75. Conclusions Gut microbiota during early pregnancy was associated with subsequent risk of GDM. Several beneficial and commensal gut microorganisms showed inverse relations with incident GDM, while opportunistic pathogenic members were related to higher risk of incident GDM and positively correlated with glucose levels on OGTT.

To analyze the association of long-term exposure to air pollution and its attributable risks with the number of tuberculosis (TB) cases notified, a quasi-Poisson regression model combined with a distributed lag nonlinear model (DLNM) was constructed using monthly data on air pollution and TB cases notified in Hong Kong from 1999 to 2018. Nonlinear relationships between PM10, PM2.5, and CO and TB cases notified were identified. The concentrations of PM10, PM2.5, and CO corresponding to the minimum numbers of TB cases notified (the minimum TB notification concentrations, MTNCs) were 58.3 μg/m3, 41.7 μg/m3, and 0.1 mg/m3, respectively. Compared with the MTNCs, the overall cumulative numbers of TB cases notified increased by 76.93% (95% CI: 13.08%, 176.83%), 88.81% (95% CI: 26.09%, 182.71%), and 233.43% (95% CI: 13.56%, 879.03%) for the 95th percentiles of PM10 and PM2.5 and for the 97.5th percentiles of CO, respectively. The TB notification rate attributed to concentration ranges above the 97.5th percentile of PM10, PM2.5, and CO was 3.38% (95% empirical confidence intervals [eCI]: 0.93%, 5.61%), 4.73% (95% eCI: 1.87%, 7.15%), and 3.34% (95% eCI: 0.29%, 5.83%), respectively. Long-term exposure to high concentrations of air pollution in Hong Kong may be associated with increases in the number of TB cases notified for this area.

ObjectivesPrevious studies suggested the association of air pollution with initialMycobacterium tuberculosisinfection and the disease development. However, few studies have been conducted on air pollution and initial tuberculosis (TB) consults using short-interval data. We investigated the weekly association between air pollution and initial TB outpatient visits.MethodsWe used a Poisson regression model combined with a distributed lag non-linear model to conduct a time-series study with weekly air pollution data and TB cases during 2014–2017 in Wuhan, China.ResultsA 10 µg/m3increase in NO2(nitrogen dioxide) was associated with 11.74% (95% CI: 0.70 to 23.98, lag 0–1 weeks), 21.45% (95% CI: 1.44 to 45.41, lag 0–2 weeks) and 12.8% (95% CI: 0.97 to 26.02, lag 0–1 weeks) increase in initial TB consults among all patients with TB, old patients (≥60 years old) and male ones, respectively. A 10 µg/m3increase in SO2(sulfur dioxide) was associated with −22.23% (95% CI: −39.23 to −0.49, lag 0–16 weeks), −28.65% (95% CI: −44.3 to −8.58, lag 0–16 weeks), −23.85 (95% CI: −41.79 to −0.37, lag 0–8 weeks) and −23.82% (95% CI: −41.31 to −1.11, lag 0–16 weeks) increase in initial TB consults among the total, young (aged 15–59 years old), old and male patients, respectively. In old patients, a 0.1 mg/m3increase in CO (carbon monoxide) and a 10 µg/m3increase in PM2.5(particulate matter) were separately associated with 42.32% (95% CI: 1.16 to 100.22, lag 0–16 weeks) and 17.38% (95% CI: 0.28 to 37.38, lag 0–16 weeks) increases in TB consults.ConclusionOur study first highlighted the importance of weekly association between air pollution and the risk of initial TB consults, which is helpful for the arrangements of TB screening and medical assistance.